Understanding brain plasticity is a major challenge facing the neurosciences. One class of animal models useful for these studies involves brain changes that occur naturally in response to salient environmental stimuli that regulate seasonal variation in reproductive physiology. Seasonal changes in the brain of songbirds are one of the most dramatic examples of this natural neuroplasticity. This proposal analyzes the anatomical circuits and cellular events that mediate the effects of steroid hormones on singing behavior and on the morphological plasticity of song control nuclei and investigates the possible effects of singing on brain plasticity. Aim I will determine whether steroids act directly on neurons that are active during singing (Expt 1). Aim II concerns the role of catecholamines in song production by analyzing the relationships among tyrosine hydroxylase-immunoreactive inputs to song control nuclei, immediate early gene expression (IEG) and steroid receptors (Expts 2-4). Aims III and IV will investigate steroid controls of cellular signals that are implicated in the recruitment and survival of new neurons that contribute to seasonal changes in the brain. Aim III will analyze whether steroids act directly on cells that produce Brain Derived Neurotrophic Factor (BDNF) and will investigate the effects of singing on BDNF expression in song nuclei (Expts 5-6). Exp 7 will test with antisense techniques whether singing-induced IEG expression is required for the stimulaton of BDNF production. Reelin, a glycoprotein that plays a key role in neuronal positioning during ontogeny, was recently shown to be present and regulated by testosterone (T) in song nucleus HVc in adult birds. Aim IV will explore the role of reelin in the recruitment of new neurons into HVc by determining whether reelin receptors are present in newborn HVc neurons (Expt 8), characterizing the effects of T on reelin expression (Expts 9-12) and assessing the effects on neuronal incorporation of manipulations of reelin expression (Expt 13). Aim V (expt 14) will investigate whether the seasonal dissociations between the effects of T on song and on the growth of song control nuclei can be explained by the uncoupling of the response to T of some of the cellular responses investigated in the initial phases of the project. These studies will provide an integrated view of cellular mechanisms that mediate song expression and the associated seasonal neuroplasticity and will contribute to an understanding of whether brain changes can be mediated via changes in behavioral expression.